Mammalian Hibernation Research- A Path Towards a Center for Transformative Research in Metabolism

哺乳动物冬眠研究——通往代谢转化研究中心的道路

基本信息

批准号：
10455075
负责人：
KELLY L DREW
金额：
$ 230.77万
依托单位：
UNIVERSITY OF ALASKA FAIRBANKS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-16 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10455075
关键词：
Address Adopted Adult Alaska Animals Arctic Regions Arousal Basal metabolic rate Basic Science Biology Biomedical Research Black Bear Body Composition Body Temperature Cardiovascular Diseases Centers of Research Excellence Cessation of life Clinical Clinical Research Clinical Trials Complex Desire for food Diet Eating Elderly Essential Amino Acids Fasting Foundations Funding Genetic Goals Health Health Care Costs Heart Arrest Hibernation Homeostasis Hospitalization Hour Human Impairment Individual Institutes Interdisciplinary Study Knowledge Laboratories Leadership Legal patent Life Link Mammals Metabolic Metabolic Diseases Metabolism MicroRNAs Modeling Muscular Atrophy Non-Insulin-Dependent Diabetes Mellitus Obesity Patients Phase Phase 0 Study Physiological Pilot Projects Play Population Post-Transcriptional Regulation Pre-Clinical Model Prophylactic treatment Protein Biosynthesis Regulation Research Research Infrastructure Research Personnel Research Project Grants Research Support Role Scientist Seizures Skeletal Muscle Source Spermophilus Stroke Temperature Time Transcript Translating Translations United States National Institutes of Health Universities arctic ground squirrel career career development design differential expression disability risk druggable target experience flexibility gut microbiota improved indexing insight interest metabolic rate microbial multidisciplinary muscle form muscle strength obese person organizational structure preservation research and development response sarcopenia skeletal muscle growth skeletal muscle metabolism skeletal preservation

项目摘要

Project Summary - Overall This application is in response to PAR-16-415, Centers of Biomedical Research Excellence (COBRE) (P20). The proposed phase 1 center (P1C) is built on a strong foundation and long-term commitment to hibernation research at the University of Alaska's Institute of Arctic Biology (IAB). The objective of the P1C is to use the expertise at IAB, in particular that of Dr. Kelly Drew, the PI, to build and strengthen the University of Alaska's hibernation research infrastructure. The plan involves guiding the career development of three investigators, experienced in research, but who have yet to receive R01s from NIH, and to guide the career development of new investigators currently showing an interest in hibernation research. The long-term goal, likely beyond the life of the P1C, is to apply what is learned about the mechanisms underlying the physiological changes in hibernation to as yet unresolved issues relevant to metabolism and metabolic diseases such as disuse muscle atrophy, sarcopenia, obesity, type 2 diabetes and cardiovascular diseases in humans. The center will support the research and career development of both experienced scientists and those getting their start in research. The center will have a focus on all stages of research from basic through translational. By defining translational paths for discoveries in hibernation, the P1C will contribute to the career development of the investigators. Strong administrative and scientific leadership will accomplish the goals of this P1C through the following four Specific Aims (SA): SA1. Establish an organizational structure and research infrastructure that will support and promote a multidisciplinary framework to define mechanisms of metabolic adaptations in hibernating mammals. SA 2. Enhance the careers of P1C project PIs as well as new investigators leading pilot projects through the P1C in order to allow them to compete successfully for NIH individual research grants. SA3. Support research projects and pilot projects aimed at developing an understanding of physiological, genetic and gut microbial mechanisms in hibernation and how these mechanisms may play a role in treating disuse muscle atrophy or sarcopenia. SA 4. Support clinical research projects related to the theme of the center. Seasonal hibernators arguably display the most dramatic natural alterations in metabolism, appetite, diet, body composition and body temperature of any mammal across their annual cycle. Such extremes offer insight into regulatory mechanisms, and druggable targets that would be less obvious in traditional pre-clinical models. This P1C focuses on genetic and gut microbial mechanisms related to protein synthesis and preservation of skeletal muscle during prolonged disuse and fasting in hibernating mammals. Once completed new investigators will be equipped to identify and translate treatments to promote anabolic sensitivity and preservation of muscle mass and strength. Such discoveries have the potential to save $1 billion per year in health-care costs in the US by reducing risk for disability, hospitalization, and death in older and mobility impaired adults.

项目总结 - 总体此应用程序是为了响应 PAR-16-415、生物医学卓越研究中心 (COBRE) (P20)。拟议的第一阶段中心（P1C）建立在坚实的基础和对冬眠的长期承诺之上阿拉斯加大学北极生物学研究所（IAB）的研究。 P1C 的目标是使用 IAB 的专业知识，特别是 PI 凯利·德鲁 (Kelly Drew) 博士的专业知识，旨在建设和加强阿拉斯加大学冬眠研究基础设施。该计划涉及指导三名研究者的职业发展，有研究经验，但尚未获得 NIH 的 R01，并指导其职业发展新的研究人员目前对冬眠研究表现出兴趣。长期目标可能超出 P1C 的生命，就是应用所学到的有关生理变化背后的机制的知识冬眠与代谢和代谢疾病（例如废用性肌肉）相关的尚未解决的问题人类萎缩、肌肉减少症、肥胖、2 型糖尿病和心血管疾病。中心将支持经验丰富的科学家和刚开始研究的科学家的研究和职业发展。该中心将重点关注从基础到转化的所有研究阶段。通过定义平移 P1C 将为研究者的职业发展做出贡献。强有力的行政和科学领导将通过以下四个方面实现本次 P1C 的目标具体目标 (SA)：SA1。建立组织结构和研究基础设施，以支持和促进多学科框架来定义冬眠哺乳动物的代谢适应机制。 SA 2. 通过以下方式增强 P1C 项目 PI 以及领导试点项目的新研究者的职业生涯 P1C，以便让他们能够成功竞争 NIH 个人研究资助。 SA3。支持研究旨在加深对生理、遗传和肠道微生物的了解的项目和试点项目冬眠机制以及这些机制如何在治疗废用性肌肉萎缩或肌肉减少症。 SA 4.支持与中心主题相关的临床研究项目。季节性冬眠者可以说在新陈代谢、食欲、饮食、身体成分和任何哺乳动物在其年度周期中的体温。这种极端情况提供了对监管的洞察机制和药物靶标在传统的临床前模型中不太明显。这个P1C 专注于与蛋白质合成和骨骼保存相关的遗传和肠道微生物机制冬眠哺乳动物长时间不用和禁食时的肌肉。一旦完成，新的调查人员将能够识别和转化治疗方法，以促进合成代谢敏感性和肌肉质量的保存和力量。这些发现有可能为美国每年节省 10 亿美元的医疗费用降低老年人和行动不便的成年人残疾、住院和死亡的风险。